This work was done in part with government funding under United States Public Health Service Grants CA-32516, HL-31780, CA-20194, CA-23766 and CA-00966. Therefore the government has certain rights in this invention.
Abbreviations
CFU-GEMM: Colony forming unit--granulocyte, erythroid, macrophage, megakaryocyte. PA1 CFU-GM: Colony forming unit--granulocyte-macrophage PA1 BFU-E: erythroid burst forming unit PA1 GM-CSF: Granulocyte-macrophage colony stimulating factor
Colony-stimulating factors (CSFs) are hormone-like glycoproteins produced by a variety of tissues and tumor cell lines which regulate hematopoiesis and are required for the clonal growth and maturation of normal bone marrow cell precursors in vitro (Burgess, A. W., et al. (1980) Blood 56:947-958; Nicola, N. A., et al. (1984) Immunology Today 5:76-81). In contrast to the murine system (Nicola, N. A., et al. (1983) J. Biol. Chem. 258:9017-9021; Ihle, J. N., et al. (1982) J. Immunol. 129:2431-2436; Fung, M. C., et al. (1984) Nature 307:233-237; Gough, N. M., et al. (1984) Nature 309:763-767), human CSFs have been less well characterized, both biologically and biochemically (Nicola, N. A., et al. (1979) Blood 54:614-627; Wu, M. C., et al. (1980) J. Clin. Invest. 65:772-775; Golde, D. W., et al. (1980) Proc. Nat'l. acad. Sci. USA 77:593-596; Lusis, A. J., et al. (1981) Blood 57:13-21; Abboud, C. N., et al. (1981) Blood 58:1148-1154; Okabe, T., et al. (1982) J. Cell. Phys. 110:43-49). Purification to apparent homogeneity has only been reported for macrophage active CSF (CSF-1) (Das, S. K., et al. (1981) Blood 58:630-641; Das, S. K., et al. (1982) J. Biol. Chem. 257:13679-13684) and erythroid potentiating activity [Westbrook, C. A. et al. J. Biol. Chem. 259:9992-9996 (1984)] and for granulocyte-macrophage CSF (GM-CSF) [Gasson, J. C., et al. Science 226:1339-1342 (1984)], but not for human pluripotent CSF.
Assays are available to detect human clonogenic precursors that give rise to cells of the erythroid, granulocytic, megakaryocytic, macrophage (CFU-GEMM) (Fauser, A. A., et al. (1978) Blood 52:1243-1248; Fauser, A. A., et al. (1979) Blood 53:1023-1027) and possibly lymphoid (Messner, H. A., et al. (1981) Blood 58:402-405) lineages. CSFs with activities on these multipotential progenitor cells (pluripotent CSF or P-CSF) are produced by mitogen- or antigen activated T lymphocytes (Ruppert, S., et al. (1983) Exp. Hematol. 11:154-161) and constitutively by human tumor cell lines such as the SK-HEP-1 human hepatoma cell line (J. Gabrilove, K. Welte, Li Lu, H. Castro-Malaspina, M. A. S. Moore, Blood, in Press and hereby incorporated by reference); the 5637 bladder carcinoma cell line (reported herein and in Proc. Nat'l. Acad. Sci. 82:1526-1530 1985 hereby incorporated by reference); and by the HTLV-transformed lymphoid cells (Fauser, A. A., et al. (1981) Stem Cells 1:73-80; Salahuddin, S. Z., et al. (1984) Science 223:703-707). Pluripotent CSF is involved in the proliferation and differentiation of pluripotent progenitor cells leading to the production of all major blood cell types. This is therefore a broad spectrum CSF. It also induces differentiation of leukemic cells.